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1.
Expert Rev Mol Diagn ; 16(7): 723-32, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27095565

RESUMO

INTRODUCTION: Laboratory diagnosis of HIV infection is essential for the prevention of infection and the identification of infected individuals who could benefit from highly active antiretroviral therapy. Since the release of the first assays for the detection of anti-HIV antibodies, the technology of immunoassays has improved. AREAS COVERED: Fourth generation assays - simultaneously detecting HIV p24 antigen and antibodies - have been developed and have been a major improvement in the detection of HIV infection, with a reduction of the diagnostic window. Studies have provided definite evidence for their clinical utility. Combination assays with separate results for anti-HIV antibodies and p24 antigen have been developed. Expert Commentary: In conclusion, fourth generation assays are an effective tool for the laboratory diagnosis of HIV infection. The ADVIA Centaur HIV Ag/Ab Combo assay is in line with most recent fourth generation assays and its clinical utility has been assessed.


Assuntos
Sorodiagnóstico da AIDS/métodos , ELISPOT/métodos , Infecções por HIV/sangue , Técnicas de Diagnóstico Molecular/métodos , Infecções por HIV/imunologia , Humanos , Sensibilidade e Especificidade
2.
Biosens Bioelectron ; 80: 590-600, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-26896794

RESUMO

We report an innovative fiber optic nano-optrode based on Long Period Gratings (LPGs) working in reflection mode for the detection of human Thyroglobulin (TG), a protein marker of differentiated thyroid cancer. The reflection-type LPG (RT-LPG) biosensor, coated with a single layer of atactic polystyrene (aPS) onto which a specific, high affinity anti-Tg antibody was adsorbed, allowed the label-free detection of Tg in the needle washouts of fine-needle aspiration biopsies, at concentrations useful for pre- and post-operative assessment of the biomarker levels. Analyte recognition and capture were confirmed with a parallel on fiber ELISA-like assay using, in pilot tests, the biotinylated protein and HRP-labeled streptavidin for its detection. Dose-dependent experiments showed that the detection is linearly dependent on concentration within the range between 0 and 4 ng/mL, while antibody saturation occurs for higher protein levels. The system is characterized by a very high sensitivity and specificity allowing the ex-vivo detection of sub ng/ml concentrations of human Tg from needle washouts of fine-needle aspiration biopsies of thyroid nodule from different patients.


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Técnicas Biossensoriais , Tireoglobulina/isolamento & purificação , Neoplasias da Glândula Tireoide/diagnóstico , Biomarcadores Tumorais/genética , Biópsia por Agulha Fina , Tecnologia de Fibra Óptica , Humanos , Neoplasias da Glândula Tireoide/genética
3.
Intervirology ; 59(4): 211-216, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28278509

RESUMO

OBJECTIVE: Human cytomegalovirus (CMV) can be considered the most important agent of congenital infection. Long-term sequelae of congenital infection occur in about 15% of infants asymptomatic at birth. To avoid long-term sequelae or to reduce their burden, it is necessary to identify infected children for early interventions. CMV DNA can be detected in dried blood spots (DBSs). DBSs have been used in several studies for the retrospective diagnosis of congenital CMV (CCMV). It has been proposed to use DBSs for the newborn screening of CMV infection; however, manual methods are not suitable for newborn screening of CCMV. METHODS: We evaluated in an off-label application the use of an automated instrument, the QIAsymphony SP/AS, in combination with the artus CMV QS-RGQ kit and the RotorGene Q real-time polymerase chain reaction system. RESULTS: We analyzed 100 DBSs from newborns positive or negative for plasma CMV DNA with a 94% concordance in positive samples. CONCLUSIONS: We show that the QIAsymphony SP/AS and RotorGene Q workflow is suitable for CMV DNA extraction and detection from DBSs and that the system correctly identified newborns at risk of late sequelae due to CMV infection.


Assuntos
Automação , Infecções por Citomegalovirus/sangue , Citomegalovirus/genética , DNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Fluxo de Trabalho , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/virologia , DNA Viral/genética , Teste em Amostras de Sangue Seco/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Sensibilidade e Especificidade , Carga Viral/genética
4.
Ital J Pediatr ; 41: 14, 2015 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-25887861

RESUMO

BACKGROUND: A relationship between low levels of serum vitamin D and respiratory infections has been established. No study has examined the frequency and clinical relevance of vitamin D deficiency in patients with primary ciliary dyskinesia (PCD). METHODS: Vitamin D levels were measured in 22 PCD patients (7 females, 10.5 years, range, 2-34 years). In PCD, pulmonary function tests (PFTs), sputum microbiology, self-reported physical activity (PA) level, and quality of life (QoL) by means of the Saint George's Respiratory Questionnaire (SGRQ), were also assessed. RESULTS: Seventy-two percent of PCD patients were vitamin-D deficient-to-insufficient and 28% were sufficient. No differences in PFTs parameters were found between vitamin D deficiency-to-insufficiency and sufficiency groups. Patients with vitamin D deficiency-to-insufficiency had significantly higher SGRQ total scores, and thus poorer QoL (p = 0.03). Seventy-nine percent of PCD subjects had limitations in performing vigorous activities, and 53% performed less than 3 hours of PA per week. Vitamin D deficiency-to-insufficiency and sufficiency groups did not show any differences in age at PCD diagnosis or at onset of respiratory symptoms, BMI, atopy, current asthma or bronchiectasis. However, 79% of patients with bronchiectasis had vitamin D deficiency-to-insufficiency. No differences were found in the rate of positive sputum cultures and in the number of antibiotic courses between the two groups. CONCLUSIONS: Hypovitaminosis D is common in PCD patients, and is associated with poorer QoL. We recommend the assessment and treatment of hypovitaminosis D to be included in the routine management of PCD.


Assuntos
Síndrome de Kartagener/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adolescente , Adulto , Bronquiectasia/epidemiologia , Criança , Pré-Escolar , Comorbidade , Estudos Transversais , Feminino , Humanos , Síndrome de Kartagener/sangue , Síndrome de Kartagener/patologia , Masculino , Atividade Motora , Qualidade de Vida , Adulto Jovem
5.
Urol Int ; 94(4): 373-82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25765848

RESUMO

BACKGROUND: Radical external beam radiotherapy (EBRT) is a standard treatment for prostate cancer patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. For these patients, local salvage therapy such as radical prostatectomy, cryotherapy, and brachytherapy may be indicated. OBJECTIVE: The objectives of this review were to analyze the eligibility criteria for careful selection of appropriate patients and to evaluate the oncological results and complications for each method. METHODS: A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. RESULTS: Most studies demonstrated that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. CONCLUSIONS: Our results suggest that for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis. An improvement in selection criteria and an integrated definition of biochemical failure for all salvage methods are required to determine which provides the best oncological outcome and least comorbidity.


Assuntos
Recidiva Local de Neoplasia , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Terapia de Salvação , Humanos , Masculino , Seleção de Pacientes , Prostatectomia/efeitos adversos , Prostatectomia/mortalidade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
6.
Anticancer Res ; 35(2): 1017-23, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25667489

RESUMO

BACKGROUND/AIM: Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. MATERIALS AND METHODS: The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. RESULTS: We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). CONCLUSION: PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS).


Assuntos
Antígenos de Neoplasias/metabolismo , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Sarcosina/metabolismo , Humanos , Masculino , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Curva ROC
8.
Dev Comp Immunol ; 48(1): 129-37, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25305501

RESUMO

In humans, IL-17 is a proinflammatory cytokine that plays a key role in the clearance of extracellular bacteria promoting cell infiltration and production of several cytokines and chemokines. Here, we report on three Ciona intestinalis IL-17 homologues (CiIL17-1, CiIL17-2, CiIL17-3). The gene organization, phylogenetic tree and modeling supported the close relationship with the mammalian IL-17A and IL-17F suggesting that the C. intestinalis IL-17 genes share a common ancestor in the chordate lineages. Real time PCR analysis showed a prompt expression induced by LPS inoculation suggesting that they are involved in the first phase of inflammatory response. In situ hybridization assays disclosed that the genes transcription was upregulated in the pharynx, the main organ of the ascidian immune system, and expressed by hemocytes (granulocytes and univacuolar refractile granulocyte) inside the pharynx vessels.


Assuntos
Ciona intestinalis/imunologia , Interleucina-17/genética , Isoformas de Proteínas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Hemócitos/metabolismo , Humanos , Inflamação/imunologia , Interleucina-17/biossíntese , Lipopolissacarídeos/farmacologia , Dados de Sequência Molecular , Filogenia , Isoformas de Proteínas/biossíntese , Alinhamento de Sequência , Análise de Sequência de DNA
9.
Transl Res ; 164(6): 444-51, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25035153

RESUMO

The most promising approach to improve the specificity of prostate-specific antigen (PSA) test relies on the measurement of different molecular isoforms of PSA in serum. Currently, in men with a total PSA (tPSA) level between 2 and 10 ng/mL, measurement of %fPSA (free to total PSA ratio ×100) is used as reflex testing to better distinguish between malignant and benign prostate disease. Recently, Beckman Coulter developed the prostate health index (PHI) and several studies suggested that this test may improve the diagnostic ability of %fPSA.We performed a meta-analysis to evaluate the usefulness of PHI compared with %fPSA in the detection of prostate cancer (PCa) at first biopsy in men with tPSA "gray" levels of 2-10 ng/mL. Data on sensitivity and specificity were extracted from 8 eligible studies. Only observational studies comparing the diagnostic ability of PHI and %fPSA in tPSA range of 2-10 ng/mL were included. A total of 8 studies involving 2969 patients with a tPSA range of 2-10 ng/mL undergoing first biopsy were included in this meta-analysis. Biopsy-confirmed PCa was detected in 1287 (43.3%) men. Selected studies determined both PHI and %fPSA as a reflex test. The areas under curve (AUCs) of PHI and %fPSA were 0.74 (95% confidence interval [CI], 0.70-0.77) and 0.63 (95% CI, 0.58-0.67), respectively. Meta-regression analysis confirmed the superiority of PHI which showed, compared with %fPSA, a relative diagnostic odds ratio of 2.81 (95% CI, 2.19-3.6; P < 0.0001). In conclusion, PHI instead of %fPSA as a reflex test in men with tPSA "gray" levels is a better predictor of positive first biopsy and can offer a reduction in unnecessary biopsies.


Assuntos
Antígeno Prostático Específico/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Biópsia , Humanos , Masculino , Curva ROC , Sensibilidade e Especificidade , Inquéritos e Questionários
10.
Intervirology ; 57(2): 106-11, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24557036

RESUMO

Fourth-generation assays for the simultaneous detection of human immunodeficiency virus (HIV) antigen and antibodies are available on the international market and are currently used for blood donor screening and for HIV diagnosis. In this study we evaluated the performance of the novel automated fourth-generation ADVIA Centaur® HIV Ag/Ab Combo assay. The assay detected seroconversion at the same bleed or at least one bleed earlier in panels with respect to other assays and showed a detection efficacy equal to those of other assays in a low-titer panel. Samples obtained from blood donors (n = 2,778) or from HIV-positive patients (HIV-1 B subtype, n = 82; non-B subtype, n = 71) were also tested, showing a good correlation with other fourth-generation assays. We assessed the performance of 3 fourth-generation assays for detecting in utero transmitted anti-HIV antibodies and found a more specific detection efficiency with the ADVIA Centaur HIV Ag/Ab Combo assay compared to the other fourth-generation assays.


Assuntos
Técnicas de Laboratório Clínico/métodos , Anticorpos Anti-HIV/sangue , Antígenos HIV/sangue , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Automação Laboratorial/métodos , Feminino , Infecções por HIV/virologia , HIV-1/imunologia , Humanos , Imunoensaio/métodos , Recém-Nascido , Masculino , Programas de Rastreamento/métodos , Gravidez , Sensibilidade e Especificidade
11.
PLoS One ; 8(7): e67687, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23861782

RESUMO

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA.


Assuntos
Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Antígeno Prostático Específico/genética , Próstata/metabolismo , Neoplasias da Próstata/diagnóstico , Projetos de Pesquisa , Idoso , Antígenos de Neoplasias/sangue , Área Sob a Curva , Biomarcadores Tumorais/sangue , Biópsia , Diagnóstico Precoce , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Curva ROC
12.
BMC Cancer ; 13: 81, 2013 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-23421821

RESUMO

BACKGROUND: The human ERBB2 gene is frequently amplified in breast tumors, and its high expression is associated with poor prognosis. We previously reported a significant inverse correlation between Myc promoter-binding protein-1 (MBP-1) and ERBB2 expression in primary breast invasive ductal carcinoma (IDC). MBP-1 is a transcriptional repressor of the c-MYC gene that acts by binding to the P2 promoter; only one other direct target of MBP-1, the COX2 gene, has been identified so far. METHODS: To gain new insights into the functional relationship linking MBP-1 and ERBB2 in breast cancer, we have investigated the effects of MBP-1 expression on endogenous ERBB2 transcript and protein levels, as well as on transcription promoter activity, by transient-transfection of SKBr3 cells. Reporter gene and chromatin immunoprecipitation assays were used to dissect the ERBB2 promoter and identify functional MBP-1 target sequences. We also investigated the relative expression of MBP-1 and HDAC1 in IDC and normal breast tissues by immunoblot analysis and immunohistochemistry. RESULTS: Transfection experiments and chromatin immunoprecipitation assays in SKBr3 cells indicated that MBP-1 negatively regulates the ERBB2 gene by binding to a genomic region between nucleotide -514 and -262 of the proximal promoter; consistent with this, a concomitant recruitment of HDAC1 and loss of acetylated histone H4 was observed. In addition, we found high expression of MBP-1 and HDAC1 in normal tissues and a statistically significant inverse correlation with ErbB2 expression in the paired tumor samples. CONCLUSIONS: Altogether, our in vitro and in vivo data indicate that the ERBB2 gene is a novel MBP-1 target, and immunohistochemistry analysis of primary tumors suggests that the concomitant high expression of MBP-1 and HDAC1 may be considered a diagnostic marker of cancer progression for breast IDC.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/metabolismo , Proteínas de Ligação a DNA/metabolismo , Genes erbB-2 , Histona Desacetilase 1/metabolismo , Proteínas de Neoplasias/metabolismo , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Histona Desacetilase 1/genética , Humanos , Imuno-Histoquímica , Proteínas de Neoplasias/genética , Regiões Promotoras Genéticas , Receptor ErbB-2/metabolismo , Células Tumorais Cultivadas
13.
Prostate ; 73(3): 227-35, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22821756

RESUMO

BACKGROUND: Prostate health index (phi) and prostate cancer antigen 3 (PCA3) have been recently proposed as novel biomarkers for prostate cancer (PCa). We assessed the diagnostic performance of these biomarkers, alone or in combination, in men undergoing first prostate biopsy for suspicion of PCa. METHODS: One hundred sixty male subjects were enrolled in this prospective observational study. PSA molecular forms, phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay), and other established biomarkers (tPSA, fPSA, and %fPSA) were assessed before patients underwent a 18-core first prostate biopsy. The discriminating ability between PCa-negative and PCa-positive biopsies of Beckman coulter phi and PCA3 score and other used biomarkers were determined. RESULTS: One hundred sixty patients met inclusion criteria. %p2PSA (p2PSA/fPSA × 100), phi and PCA3 were significantly higher in patients with PCa compared to PCa-negative group (median values: 1.92 vs. 1.55, 49.97 vs. 36.84, and 50 vs. 32, respectively, P ≤ 0.001). ROC curve analysis showed that %p2PSA, phi, and PCA3 are good indicator of malignancy (AUCs = 0.68, 0.71, and 0.66, respectively). A multivariable logistic regression model consisting of both the phi index and PCA3 score allowed to reach an overall diagnostic accuracy of 0.77. Decision curve analysis revealed that this "combined" marker achieved the highest net benefit over the examined range of the threshold probability. CONCLUSIONS: phi and PCA3 showed no significant difference in the ability to predict PCa diagnosis in men undergoing first prostate biopsy. However, diagnostic performance is significantly improved by combining phi and PCA3.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Próstata/patologia , Próstata/fisiologia , Neoplasias da Próstata/diagnóstico , Idoso , Biópsia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Curva ROC , Sensibilidade e Especificidade
14.
Clin Chim Acta ; 413(15-16): 1274-8, 2012 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-22542564

RESUMO

Indication for prostate biopsy is presently mainly based on prostate-specific antigen (PSA) serum levels and digital-rectal examination (DRE). In view of the unsatisfactory accuracy of these two diagnostic exams, research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as phi and PCA3. The purpose of this prospective study was to assess the diagnostic accuracy of phi and PCA3 for prostate cancer using biopsy as gold standard. Phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay) and other established biomarkers (tPSA, fPSA and %fPSA) were assessed before a 18-core prostate biopsy in a group of 251 subjects at their first biopsy. Values of %p2PSA and phi were significantly higher in patients with PCa compared with PCa-negative group (p<0.001) and also compared with high grade prostatic intraepithelial neoplasia (HGPIN) (p<0.001). PCA3 score values were significantly higher in PCa compared with PCa-negative subjects (p<0.001) and in HGPIN vs PCa-negative patients (p<0.001). ROC curve analysis showed that %p2PSA, phi and PCA3 are predictive of malignancy. In conclusion, %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men undergoing their first prostate biopsy. PCA3 score is more useful in discriminating between HGPIN and non-cancer.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia , Exame Retal Digital , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia
15.
Prostate ; 72(1): 100-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21520165

RESUMO

BACKGROUND: About 43% of men with low Gleason grade prostate cancer (PCa) at biopsy will be finally diagnosed with high-grade PCa at radical prostatectomy (RP). Gleason sum at RP is a good indicator of biochemical recurrence and poor clinical outcome. Therefore, there is a need to improve clinical evaluation of PCa aggressiveness in order to choice appropriate treatment. To this aim an easy-available tool is represented by circulating biomarkers. Among these, the best candidates are some molecules involved in PCa pathogenesis such as IGFBP-2 and IGFBP-3, IL-6, and its soluble receptor (SIL-6R). METHODS: In this study, we evaluated the ability of preoperative IGFBP-2, IGFBP-3, IL-6, and SIL-6R serum levels to predict Gleason score upgrade in 52 PCa patients. RESULTS: We found that IGFBP-3 median levels were significantly lower in patients who showed Gleason upgrading from biopsy to RP (P = 0.024). We also found an association between biopsy T-stage and Gleason Upgrade (P = 0.011). Using multivariate logistic regression model, we demonstrated that the association of IGFBP-3 serum levels together with biopsy T-stage and biopsy Gleason score was useful to calculate a prognostic risk score. ROC curve analysis of risk score showed a good ability to predict GSU (AUC = 0.81; 95% CI 0.69-0.93). CONCLUSIONS: Our results suggest that preoperative IGFBP-3 circulating levels determination may be useful to predict Gleason score upgrading alone and/or in combination with biopsy T-stage and biopsy Gleason score.


Assuntos
Adenocarcinoma/patologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Próstata/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/sangue , Adenocarcinoma/cirurgia , Idoso , Humanos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Período Pré-Operatório , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/cirurgia , Receptores de Interleucina-6/sangue
16.
PLoS One ; 5(9): e12961, 2010 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-20886042

RESUMO

BACKGROUND: Alpha-enolase is a glycolytic enzyme that catalyses the formation of phosphoenolpyruvate in the cell cytoplasm. α-Enolase and the predominantly nuclear Myc promoter-binding protein-1 (MBP-1) originate from a single gene through the alternative use of translational starting sites. MBP-1 binds to the P2 c-myc promoter and competes with TATA-box binding protein (TBP) to suppress gene transcription. Although several studies have shown an antiproliferative effect of MBP-1 overexpression on several human cancer cells, to date detailed observations of α-enolase and MBP-1 relative expression in primary tumors versus normal tissues and their correlation with clinicopathological features have not been undertaken. METHODOLOGY AND FINDINGS: We analyzed α-enolase and MBP-1 expression in normal breast epithelium and primary invasive ductal breast carcinoma (IDC) from 177 patients by Western blot and immunohistochemical analyses, using highly specific anti-α-enolase monoclonal antibodies. A significant increase in the expression of cytoplasmic α-enolase was observed in 98% of the tumors analysed, compared to normal tissues. Nuclear MBP-1 was found in almost all the normal tissues while its expression was retained in only 35% of the tumors. Statistically significant associations were observed among the nuclear expression of MBP-1 and ErbB2 status, Ki-67 expression, node status and tumor grade. Furthermore MBP-1 expression was associated with good survival of patients with IDC. CONCLUSIONS: MBP-1 functions in repressing c-myc gene expression and the results presented indicate that the loss of nuclear MBP-1 expression in a large number of IDC may be a critical step in the development and progression of breast cancer and a predictor of adverse outcome. Nuclear MBP-1 appears to be a novel and valuable histochemical marker with potential prognostic value in breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Carcinoma Ductal/diagnóstico , Carcinoma Ductal/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal/metabolismo , Carcinoma Ductal/patologia , Núcleo Celular/genética , Núcleo Celular/metabolismo , Citoplasma/enzimologia , Citoplasma/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Prognóstico , Transporte Proteico
17.
Oncol Rep ; 24(1): 213-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20514464

RESUMO

Prostate cancer is one of the most frequently diagnosed cancer in men. Treatment by radical prostatectomy, radiotherapy and anti-androgen drugs is successful in patients with localized cancer. However, prolonged androgen deprivation often leads to hormone refractory condition, associated with disease relapse. ErbB1 and ErbB2 activity has been correlated with androgen-independence. We determined the effects of GW2974, a dual inhibitor of ErbB-1 and ErbB-2 tyrosine kinase activity, on growth, NSE, chromogranin A and osteopontin cytosol content in the androgen-independent prostate cancer cell line PC-3. We found that PC-3 cell growth was inhibited by GW2974, whereas NSE and chromogranin A cell contents were stimulated and osteopontin cytosol level was not affected. The present data may have clinical implications for the treatment of advanced prostate cancer.


Assuntos
Carcinoma/patologia , Proliferação de Células/efeitos dos fármacos , Neoplasias da Próstata/patologia , Quinazolinas/farmacologia , Androgênios/farmacologia , Antineoplásicos Hormonais/farmacologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Proteínas de Transporte/análise , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Cromogranina A/análise , Cromogranina A/metabolismo , Citosol/química , Citosol/efeitos dos fármacos , Citosol/metabolismo , Avaliação Pré-Clínica de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Humanos , Masculino , Osteopontina/análise , Osteopontina/metabolismo , Neoplasias da Próstata/metabolismo , Receptor ErbB-2/antagonistas & inibidores
18.
Oncol Lett ; 1(3): 465-471, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-22966327

RESUMO

A panel of tumour markers including carcinoembryonic antigen (CEA), carbohydrate antigen (Ca)15-3, Ca125 and Ca19-9 were measured in the lysate of sediments and in the supernatants of pleural effusions of patients with benign and malignant disease. The tumour markers were also measured in the serum of the same patients. Of these patients, 32 had benign diseases (12 trasudative effusions associated with cirrhosis and 20 with non-malignant exudates: 12 pleuritis and 8 other inflammations) and 103 had malignant effusions (37 breast cancers, 29 lung cancers, 10 ovary cancers, 6 kidney cancers, 11 mesotheliomas and 10 lymphomas). We showed the highest level of CEA in pleural effusions of lung cancer followed by that in pleural effusions of breast cancer; whereas Ca15-3 was very high in the pleural effusions of breast and lung cancer. Concerning the lysate of sediment, CEA was high in the pleural effusions of patients with lung cancer and Ca15-3 in those of patients with breast cancer. The other markers are much less useful. For the remaining tumours, none of the markers tested appear to aid in the diagnosis of disease. In conclusion, our data suggest that the combined determination of tumour markers on supernatants and sediments of pleural effusion may provide additional information on the nature of pleural effusion, especially for cases with negative cytology.

19.
Nutrition ; 25(9): 926-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19647624

RESUMO

OBJECTIVE: Mild iodine deficiency was first documented in Campania in the 1990s. We assessed the urinary iodine nutritional status of schoolchildren in Campania before the introduction of legislation for salt iodization and compared the findings with previous results to evaluate to what extent "silent" iodine prophylaxis, which accompanies socioeconomic advances, affects iodine status. METHODS: We examined 10552 schoolchildren aged 9-13 y from the five Campania provinces. The study was conducted from April 1999 to October 2002. Urinary iodine excretion was measured in morning urine samples with the AutoAnalyzer 3, an automated system based on the Sandell-Kolthoff reaction. Data were interpreted according to World Health Organization criteria. RESULTS: The median urinary iodine excretion level in Campania was less than 100 micromicrog/L, which indicates insufficient iodine intake. Mild iodine deficiency was identified in all provinces, namely Napoli, Salerno, Caserta, Avellino, and Benevento, with median urinary iodine excretions of 87, 81, 72, 64, and 61 microg/L, respectively. Overall, the analysis of frequency distribution showed values below 50 and 100 microg/L in 32% and 61% of children, respectively. These values were lower than those previously reported for Campania. CONCLUSION: This study confirms that Campania is a mild iodine deficiency area. The decrease in iodine deficiency versus previous studies indicates that silent prophylaxis plays a relevant role in this condition, but it is not sufficient to eradicate it. Our data will serve as a basis for future evaluations of iodine status in Campania.


Assuntos
Iodo/deficiência , Iodo/urina , Avaliação Nutricional , Adolescente , Criança , Deficiências Nutricionais/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Estado Nutricional
20.
Dis Markers ; 26(2): 55-63, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19407360

RESUMO

BACKGROUND: Tissue Polypeptide Specific antigen has recently been proposed as diagnostic marker of apoptosis in NonAlcoholic SteatoHepatitis. The aim of this study was to validate in patients suffering from NonAlcoholic SteatoHepatitis the clinical utility of this marker after different programs of weight reduction. METHODS: Overweight/obese patients with visceral adiposity and liver histology compatible were assigned to a Calorically-Restricted diet (n = 22), a Calorically-Restricted diet plus EXercise (n = 19) or No Healthy Life Style (control group, n = 21) for six months. The presence of Body-Weight loss was assessed by a Body Mass Index decrease of at least three points. Serum ALanine aminoTransferase, HOmeostasis Model Assessment method value and Tissue Polypeptide Specific antigen concentrations were determined at time 0, after 3 and 6 months in both the Intervention groups and in the controls' one. RESULTS: In NonAlcoholic SteatoHepatitis patients who obtained Body-Weight reduction, a significant decrease of the serum Tissue Polypeptide Specific antigen values was showed with a clear linear trend across time, P = 0.0001. Decrement of Tissue Polypeptide Specific antigen concentrations best differentiated the Body-Weight loss from the body-weight maintenance in respect to Tissue Polypeptide Specific antigen and HOmeostasis Model Assessment method values. CONCLUSION: This study support the clinical utility of serum Tissue Polypeptide Specific antigen antigen levels in the follow-up of overweight/obese patients with NonAlcoholic SteatoHepatitis on weight reduction programs.


Assuntos
Apoptose , Biomarcadores/sangue , Fígado Gorduroso/sangue , Peptídeos/sangue , Redução de Peso , Idoso , Alanina Transaminase/sangue , Antropometria , Índice de Massa Corporal , Restrição Calórica , Estudos Transversais , Fígado Gorduroso/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/patologia , Sobrepeso/sangue , Sobrepeso/patologia , Projetos Piloto
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